Low-dose alteplase appears optimal in patients with mild acute ischaemic stroke (AIS) and a favourable risk profile.
A study led by the George Institute for Global Health used data from the international ENCHANTED study and a validation cohort from a South Korean stroke registry.
The ENCHANTED data showed patients receiving the low 0.6mg/kg dose of alteplase had similar rates of an excellent outcome – a score of 0-1 on the modified Rankin Scale at 90 days – as patients on a standard 0.9mg/kg dose (48.9% v 46.8%).
“Patients with an excellent functional outcome were significantly more likely to be young, male, of Asian ethnicity, with a mild neurological deficit, with fewer comorbidities (including previous stroke, coronary artery disease, diabetes mellitus and atrial fibrillation), and lower prior use of warfarin, aspirin, and statin therapy, at baseline,” the study found.
However only age, systolic blood pressure, baseline NIHSS score, premorbid level of function and history of AF or diabetes remained significant on multivariate analysis.
Symptomatic intracerebral haemorrhage (sICH) rates were lower in the low-dose alteplase group (1%) compared to the standard dose group (2.2%).
“Patients with sICH were significantly more likely to be older, with a severe neurological deficit, and with history of comorbidities (including hypertension, previous stroke, coronary artery disease, DM, and AF) and prior use of aspirin at baseline.”
The findings, that there was a net advantage from low-dose alteplase in younger patients, with a lower systolic BP, mild neurological deficit, and no AF, diabetes or premorbid symptoms, were supported in the validation cohort.
Dr Xia Wang, a doctoral research fellow at the George Institute, told the limbic the blood pressure finding was unexpected.
“So for example in clinical practice, patients with high blood pressure are more likely to bleed and clinicians like to use low-dose for those patients …but actually we found that it was the patients with low systolic blood pressure who are more likely to benefit from a lower dose,” she said.
The study said the low-dose alteplase has been variously adopted in Japan and other countries on the basis of some evidence that Asians were at increased risk of sICH.
However in a sub-analysis looking only at the Caucasian population, Dr Wang found similar patient characteristics predicted benefit from low-dose alteplase.
“The conclusion is that the findings are also applicable to a Caucasian population. Use of low-dose alteplase may be preferable in acute ischaemic stroke patients with a combination of favourable characteristics, including younger age, lower systolic BP, mild neurological impairment, and no AF, DM, or pre-morbid symptoms,” she said.